Quantitative tandem mass spectrometry in the clinical laboratory: Regulation and opportunity for validation of laboratory developed tests

Judith A Stone; J Grace van der Gugten

doi:10.1016/j.jmsacl.2023.03.001

Quantitative tandem mass spectrometry in the clinical laboratory: Regulation and opportunity for validation of laboratory developed tests

J Mass Spectrom Adv Clin Lab. 2023 Mar 5:28:82-90. doi: 10.1016/j.jmsacl.2023.03.001. eCollection 2023 Apr.

Authors

Judith A Stone¹, J Grace van der Gugten²

Affiliations

¹ Department of Clinical Laboratories, University of California San Francisco Health, San Francisco, CA, United States.
² Office of the Chief Medical Examiner, Government of Alberta, Edmonton, AB, Canada.

Abstract

Tandem mass spectrometry is an important analytical tool for clinical laboratories, but tests developed and validated in-house (laboratory developed tests, or LDTs) require special consideration. In late 2022, the forecast for United States (U.S.) federal regulation of LDTs changed unexpectedly when the VALID Act was not passed by the U.S. Congress. This Act would have modified the Food and Drug Administration's (FDA's) role to increase regulatory oversight for LDT providers. In this revised context, we review optimization of quantitative mass spectrometry LDT validation and suggest avenues other than an additional FDA mandate to achieve uniform best practice. Common challenges, logistical barriers, and recommendations for easing the burden of best-quality quantitative mass spectrometry LDT method validation are discussed.

Keywords: AACC, American Association for Clinical Chemistry; AMP, Association for Molecular Pathology; CAP, College of Amercian Pathologists; CLIA’88, Clinical Laboratory Improvement Amendments of 1988; CLSI, Clinical Laboratory Standards Institute; CMS, Centers for Medicare & Medicaid Services; CoA, Certificate of Analysis; FDA, Federal Drug Administration; FFDCA, Federal Food, Drug and Cosmetics Act; GC–MS, Gas Chromatography-Mass Spectrometry; HELP, U.S. Senate Committee on Health, Education, Labor & Pensions; IA, Immunoassay(s); IVD, In-vitro Device; LC-MSMS, Liquid Chromatography-Tandem Mass Spectrometry; LDT, Laboratory Developed Test; Laboratory diagnosis; Liquid chromatography-tandem mass spectrometry; MDA, Medical Device Amendments; MLS, Medical Laboratory Scientist(s); MSACL, Mass Spectrometry & Advances in the Clinical Laboratory; Method validation; QntLCMS-LDT, Quantitative LC-MSMS LDT; SOP, Standard Operating Procedure; VALID, Verifying Accurate Leading-edge IVCT Development Act of 2021; VITAL, Verified Innovative Testing in American Laboratories Act of 2021.

Publication types

Review